Nano-formulated delivery of active ingredients from traditional Chinese herbal medicines for cancer immunotherapy

Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.

Peripheral CD4^(+) T cell signatures in predicting the responses to anti-PD-1/PD-L1 monotherapy for Chinese advanced non-small cell lung cancer

Limited benefit population of immune checkpoint inhibitors makes it urgent to screen predictive biomarkers for stratifying the patients.Herein,we have investigated peripheral CD4^(+) T cell signatures in advanced non-small cell lung cancer(NSCLC)patients receiving anti-PD-1/PD-L1 treatments.It was found that the percentages of IFN-γand IL-17A secreting naïve CD4^(+) T cells(Tn),and memory CD4^(+) T cells(Tm)expressing PD-1,PD-L1 and CTLA-4 were significantly higher in responder(R)than non-responder(NonR)NSCLC patients associated with a longer progression free survival(PFS).Logistic regression analysis revealed that the baseline IFN-γ-producing CD4^(+) Tn cells and PD-1^(+)CD4^(+) Tm cells were the most significant signatures with the area under curve(AUC)value reaching 0.849.This was further validated in another anti-PD-1 monotherapy cohort.Conversely,high percentage of CTLA-4^(+)CD4^(+) Tm cells was associated with a shorter PFS in patients receiving anti-PD-L1 monotherapy.Our study therefore elucidates the significance of functional CD4^(+) Tn and Tm subpopulations before the treatment in predicting the responses to anti-PD-1 treatment in Chinese NSCLC patients.The fact that there display distinct CD4^(+) T cell signatures in the prediction to anti-PD-1 and anti-PD-L1 monotherapy from our study provides preliminary evidence on the feasibility of anti-PD-1 and anti-PD-L1 combination therapy for advanced NSCLC patients.